ArticleActa pharmacologica Sinica2014
Timosaponin A3 induces hepatotoxicity in rats through inducing oxidative stress and down-regulating bile acid transporters.
Article in Acta pharmacologica Sinica, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 42 citations in OpenAlex.
- The validation of quality attributes in Primary Human Hepatocytes Standard.Cell regeneration (London, England) · 2025Article
- The role of botanical triterpenoids and steroids in bile acid metabolism, transport, and signaling: Pharmacological and toxicological implications.Acta pharmaceutica Sinica. B · 2024Review
- Nourishing Yin traditional Chinese medicine: potential role in the prevention and treatment of type 2 diabetes.American journal of translational research · 2024Review
- The Potential Role of Timosaponin-AIII in Cancer Prevention and Treatment.Molecules (Basel, Switzerland) · 2023Review
- Mechanism of Phellodendron and Anemarrhena Drug Pair on the Treatment of Liver Cancer Based on Network Pharmacology and Bioinformatics.Frontiers in oncology · 2022Article
- Liver injury associated with acute pancreatitis: The current status of clinical evaluation and involved mechanisms.World journal of clinical cases · 2021Review
- Single cell Raman spectroscopy to identify different stages of proliferating human hepatocytes for cell therapy.Stem cell research & therapy · 2021Article
- Dihydro-stilbene gigantol relieves CClActa pharmacologica Sinica · 2020Article
- Triterpenoid Saponin AG8 fromOxidative medicine and cellular longevity · 2020Article
- Pharmacological Activity, Pharmacokinetics, and Toxicity of Timosaponin AIII, a Natural Product Isolated FromFrontiers in pharmacology · 2020Review
- Metabolomics of Aurantio-Obtusin-Induced Hepatotoxicity in Rats for Discovery of Potential Biomarkers.Molecules (Basel, Switzerland) · 2019Article
- Metabolism, pharmacokinetics, and hepatic disposition of xanthones and saponins on Zhimu treatments for exploratively interpreting the discrepancy between the herbal safety and timosaponin A3-induced hepatotoxicity.Acta pharmacologica Sinica · 2018Article
- Molecular Mechanisms Involved in Oxidative Stress-Associated Liver Injury Induced by Chinese Herbal Medicine: An Experimental Evidence-Based Literature Review and Network Pharmacology Study.International journal of molecular sciences · 2018Review
- Antibody-modified liposomes for tumor-targeting delivery of timosaponin AIII.International journal of nanomedicine · 2018Article
- Functional human induced hepatocytes (hiHeps) with bile acid synthesis and transport capacities: A novel in vitro cholestatic model.Scientific reports · 2016Article
- Inhibition of hepatic cytochrome P450 enzymes and sodium/bile acid cotransporter exacerbates leflunomide-induced hepatotoxicity.Acta pharmacologica Sinica · 2016Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimTo investigate the mechanisms underlying the hepatotoxicity of timosaponin A3 (TA3), a steroidal saponin from Anemarrhena asphodeloides, in rats.
methodsMale SD rats were administered TA3 (100 mg·kg(-1)·d(-1), po) for 14 d, and the blood and bile samples were collected after the final administration. The viability of a sandwich configuration of cultured rat hepatocytes (SCRHs) was assessed using WST-1. Accumulation and biliary excretion index (BEI) of d8-TCA in SCRHs were determined with LC-MS/MS. RT-PCR and Western blot were used to analyze the expression of relevant genes and proteins. ROS and ATP levels, and mitochondrial membrane potential (MMP) were measured. F-actin cytoskeletal integrity was assessed under confocal microscopy.
resultsTA3 administration in rats significantly elevated the total bile acid in serum, and decreased bile acid (BA) component concentrations in bile. TA3 inhibited the viability of the SCRHs with an IC50 value of 15.21±1.73 μmol/L. Treatment of the SCRHs with TA3 (1-10 μmol/L) for 2 and 24 h dose-dependently decreased the accumulation and BEI of d8-TCA. The TA3 treatment dose-dependently decreased the expression of BA transporters Ntcp, Bsep and Mrp2, and BA biosynthesis related Cyp7a1 in hepatocytes. Furthermore, the TA3 treatment dose-dependently increased ROS generation and HO-1 expression, decreased the ATP level and MMP, and disrupted F-actin in the SCRHs. NAC (5 mmol/L) significantly ameliorated TA3-induced effects in the SCRHs, whereas mangiferin (10-200 μg/mL) almost blocked TA3-induced ROS generation.
conclusionTA3 triggers liver injury through inducing ROS generation and suppressing the expression of BA transporters. Mangiferin, an active component in Anemarrhena, may protect hepatocytes from TA3-induced hepatotoxicity.
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